Rapid loss of sense of smell predicts dementia and smaller brain areas linked to Alzheimer’s disease

Summary: Loss of smell in older adults may not only predict cognitive decline, but it may also predict structural changes in brain structures linked to Alzheimer’s disease, according to a new study.

Source: University of Chicago

Although we often underestimate our ability to smell compared to our abilities to see and hear, our sense of smell provides our brain with critical information, from detecting potential hazards like smoke to recognizing the sweet smell biscuits.

Researchers at the University of Chicago Medicine have discovered another reason to appreciate our sniffers. Not only can a person’s sense of smell decline over time predict their loss of cognitive function, but it can also predict structural changes in brain regions important in Alzheimer’s disease and dementia.

The findings, based on a longitudinal study of 515 seniors published July 2 in Alzheimer’s and dementia: the journal of the Alzheimer’s Associationcould lead to the development of olfactory screening to detect cognitive impairment in patients earlier.

“This study provides another clue to how a rapid decline in smell is a very strong indicator of what will eventually occur structurally in specific regions of the brain,” said lead author Jayant M. Pinto. , MD, professor of surgery at the University of Chicago and an ENT specialist who studies olfactory and sinus diseases.

It is estimated that more than 6 million Americans have Alzheimer’s disease, which is characterized by memory loss and other symptoms, such as mood swings and difficulty performing daily tasks. Alzheimer’s disease is incurable, but certain medications can temporarily slow its symptoms.

Memory plays a vital role in our ability to recognize smells, and researchers have long known of a link between smell and dementia. The plaques and tangles that characterize tissues affected by Alzheimer’s disease often appear in olfactory and memory-associated areas before developing in other parts of the brain. It remains unclear whether this damage actually causes a person’s sense of smell to decline.

Pinto and his team wanted to see if it was possible to identify brain alterations correlated with a person’s loss of sense of smell and cognitive function over time.

“Our idea was that people whose sense of smell declined rapidly over time would be worse off — and more likely to have brain problems and even Alzheimer’s disease itself — than people who declined slowly or maintained a normal sense of smell,” Rachel said. Pacyna, a fourth-year medical student at the University of Chicago Pritzker School of Medicine and lead author of the study.

The team mined anonymized patient data from Rush University’s Memory and Aging Project (MAP), a study group started in 1997 to research chronic diseases of aging and neurodegenerative diseases such as Alzheimer’s disease. . MAP participants are seniors living in nursing homes or senior living facilities in northern Illinois and are tested annually for their ability to identify certain odors, for cognitive function and for signs of dementia , among other health parameters. Some participants also received an MRI.

UChicago Medicine scientists found that a rapid decline in a person’s sense of smell during a period of normal cognition predicted several hallmarks of Alzheimer’s disease, including smaller gray matter volume in areas of the brain related to smell and memory, poorer cognition and higher risk. dementia in these elderly people.

In fact, the risk of losing your sense of smell was similar to carrying the APOE-e4 gene, a known genetic risk factor for developing Alzheimer’s disease.

The changes were most visible in the primary olfactory regions, including the amygdala and the entorhinal cortex, which is a major entrance to the hippocampus, a critical site in Alzheimer’s disease.

“We were able to show that the volume and shape of gray matter in the olfactory and memory-associated areas of the brain of people with rapid decline in their sense of smell were smaller than those of people with less severe olfactory decline,” Pinto said.

An autopsy is the gold standard for confirming if someone had Alzheimer’s disease, and Pinto hopes to eventually expand these findings by examining brain tissue for markers of Alzheimer’s disease.

The team also hope to study the effectiveness of using smell tests in clinics – similar to how vision and hearing tests are used – as a means of screening and monitoring older people. for the signs of early dementia, and to develop new treatments.

Smell tests are an inexpensive and easy-to-use tool that consists of a series of sticks similar in appearance to felt-tip pens. Each stick is infused with a distinct scent that individuals must identify from a set of four choices.

“If we could identify people in their 40s, 50s and 60s who are at higher risk early on, we could potentially have enough information to enroll them in clinical trials and develop better drugs,” he said. Pacyna.

It shows a brain
Memory plays a vital role in our ability to recognize smells, and researchers have long known of a link between smell and dementia. Image is in public domain

The study was limited in that participants received only one MRI scan, which meant the team lacked data to determine when structural changes in the brain began or how fast brain regions have shrunk.

“We have to take our study in the context of all the risk factors we know about Alzheimer’s disease, including the effects of diet and exercise,” Pinto said.

“The sense of smell and changing the sense of smell should be important in the context of a range of factors that we believe affect the brain in health and aging.

Additionally, since most MAP participants were white, further research is needed to determine whether underrepresented populations are similarly affected. The team’s previous work has shown marked disparities by race, with African Americans facing the most severe impairment in olfactory function.

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Pinto’s previous studies have examined the sense of smell as an important marker of health decline in the elderly. His 2014 paper found that older people with no sense of smell were three times more likely to die within five years – a better predictor of death than a diagnosis of lung disease, heart failure or cancer.

Kristen Wroblewski, MS, in Public Health Sciences and Martha McClintock, PhD, Emeritus Professor David Lee Shillinglaw Distinguished Service Professor Emerita, University of Chicago Departments of Psychology and Comparative Human Development, and Duke Han, PhD, Professor of Medicine family, neurology, psychology and gerontology from the University of Southern California.

About this research news on olfaction and Alzheimer’s disease

Author: Cassandra Belek
Source: University of Chicago
Contact: Cassandre Belek – University of Chicago
Image: Image is in public domain

Original research: Free access.
“Rapid olfactory decline during aging predicts dementia and loss of GMV in AD brain regions” by Jayant M. Pinto et al. Alzheimer’s and dementia


Rapid olfactory decline during aging predicts dementia and loss of GMV in AD brain regions


Longitudinal multivariate analyzes are needed to determine whether the rate of olfactory decline during normal cognition predicts subsequent diagnoses of Alzheimer’s disease (AD) and brain dysmorphology.


Old people (not = 515) were assessed annually for odor identification, cognitive function and clinical diagnosis of dementia (max follow-up 18 years). Regional gray matter volumes (GMV) were quantified (3T MRI) in a cross-sectional subsample (not = 121). Regression models were adjusted for APOE-ε4 genotype, dementia risk factors, and demographic data.


A more rapid olfactory decline during periods of normal cognition predicted a higher incidence of MCI or later dementia (OR 1.89, 95% CI: 1.26, 2.90, p <0.01; comparable to carrying an APOE-ε4 allele) and smaller GMV in AD and olfactory regions (β=-0.11, 95% CI -0.21, -0.00).


Rapid olfactory decline during normal cognition, using repeated olfactory measures, predicted later cognitive impairment, dementia, and smaller GMVs, highlighting its potential as a simple biomarker for early disease detection. of Alzheimer’s.

Strong points

  • Rate of olfactory decline was calculated from olfactory testing at ≥ 3 time points.
  • Rapid olfactory decline predicted impaired cognition and a higher risk of dementia.
  • Neurodegeneration on 3T magnetic resonance imaging was identical in people with olfactory decline and Alzheimer’s disease.

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